Activity of beta-lactamase inhibitor combinations on Escherichia coli isolates exhibiting various patterns of resistance to beta-lactam agents

Abstract

The efficacy of the clinically available beta-lactam/beta-lactamase inhibitor combinations (amoxicillin/clavulanic acid (CA), ticarcillin/CA, amoxicillin/sulbactam, and piperacillin/tazobactam) was evaluated on 300 amoxicillin-resistant Escherichia coli isolates having the main patterns of beta-lactam resistance. The patterns, which reflect the production of various beta-lactamase enzymes, were analyzed by a principal component analysis of susceptibility to 11 beta-lactam antibiotics or beta-lactam/beta-lactamase inhibitor combinations. Sixty-two percent of strains were not very susceptible to penicillins, cephalothin, or any beta-lactam/beta-lactamase inhibitor combinations except for piperacillin/tazobactam; these strains may represent high-level broad-spectrum beta-lactamase (so-called penicillinase) production phenotype or inhibitor-resistant TEM-like enzyme production phenotype. Of the strains, 14.7% were resistant to amoxicillin and ticarcillin compatible with low-level broad-spectrum beta-lactamase production phenotype; 5.7% were cefoxitin resistant and were postulated to present a high-level cephalosporinase production phenotype; and 2.6% were resistant to cephalothin only, attributable to a low-level cephalosporinase production phenotype. Three percent of strains were intermediate or resistant to cefotaxime and may produce an extended-spectrum beta-lactamase, and the remaining strains (12 %), resistant to all tested antibiotics except for cefotaxime and piperacillin/tazobactam, were hypothesized to produce both broad-spectrum beta-lactamase plus cephalosporinase. The minimal inhibitory concentration (MIC) for these phenotype patterns indicated that combinations of CA plus amoxicillin or ticarcillin, or sulbactam plus amoxicillin, restored the activity of penicillins against phenotype 1 strains, whereas these combinations remained inactive against the other phenotype strains. Piperacillin plus tazobactam showed the best in vitro effect against the strains of all resistance phenotypes.